DESCRIPTION (Applicant's Abstract): Chronic obstructive pulmonary disease (COPD) is a slowly progressive disorder characterized by airways obstruction that lasts for at least several months. The two major causes of COPD are chronic bronchitis and emphysema. Either disorder may occur with or without airways obstruction, but airways obstruction causes impairment of lung function leading to disability and death. COPD is a major health problem in the United States and throughout the world, consistently ranking among the most common causes of death in the United States. Cigarette smoking is the primary environmental factor that increases the risk of COPD, but other environmental factors have also been implicated. However, despite a well-established role, environmental factors alone do not cause COPD. Symptomatic COPD develops in only 10-20 percent of heavy cigarette smokers, probably those with a genetic susceptibility, although common COPD susceptibility genes have yet to be identified. This project proposes a single specific aim: to localize, within the genome, a COPD susceptibility gene. The strategy proposed is to apply statistical linkage analysis to family data. Pulmonary measurements have already been collected on 159 members of 16 pedigrees and evidence supporting a COPD susceptibility gene in these pedigrees has been obtained from segregation analysis. Each of 11,995 genetic markers, which have already been genotyped on pedigree members, will be tested for evidence of linkage to the inferred COPD susceptibility gene. Evidence of linkage to one or more genetic markers will identify genomic locations of COPD susceptibility genes. The high density of markers will allow fine-mapping of the gene. Successful completion of this gene localization project is the necessary prerequisite for a project to identify and characterize a COPD susceptibility gene. Identifying a gene that when mutated increases the risk of COPD may increase understanding of pulmonary function, as well as allowing gene-carriers to be identified and made aware of their susceptibility.